Definitive treatment of prostate cancer is limited to radical surgery or radiation therapy for localized or regional disease. Gene transfer technology offers the potential for the development of new therapies for prostate cancer. The proposed project will employ the unique apoptotic agent, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and a collagen-based matrix that enhances gene delivery system to augment immune activation. Objective/hypothesis: The long-term objective of the project is to develop an effective treatment for prostate cancer. Specifically, treatment involves the viral-mediated transfer of the gene for the cytotoxic protein TRAIL into the prostate, resulting in prostate tumor cell apoptotic death and activation of systemic antitumor immunity. Specific Aims: (1) Determine the local and systemic toxicity associated with intraprostatic injection of Ad5-TRAIL delivered in Gelfoam. (2) Examine the distribution of Ad5-TRAIL within the human prostate after transperineal injection and determine the effect of transperineal injection of Ad5-TRAIL on existent prostate cancer. Study Design: The primary focus of this proposal is to conduct a phase I clinical trial using intra-prostatic injection of Ad5-TRAIL in patients with clinically localized prostate cancer. The injections will be administered in a collagen matrix (Gelfoam) which we expect will enhance delivery and distribution. The local and systemic toxicity associated with intraprostatic injection of Ad5-TRAIL will also be determined. TRAIL is an effective cytotoxic agent which affects only prostate cancer cells. The proposed studies will help develop methods to maximize gene delivery and determine the toxicity and effectiveness of localized gene transfer therapy which could provide the basis for future studies leading to a new therapeutic approach for prostate cancer. [unreadable] [unreadable]